1,720,977 research outputs found
Lung pathogenesis of Pseudomonas aeruginosa hypermutable strains from patients with cystic fibrosis
No full textThe respiratory tract of CF patients provides a selective environment favoring development and persistence of multiple P. aeruginosa pathogenic variants not eradicable by any known therapy. Whether P. aeruginosa clonal variants, including hypermutable strains, differ in their pathogenic potential is not known.
Multiple genotypic analysis were performed in strains isolated from CF patients carrying the same clonal lineage from the onset of colonization over many years. PFGE, ATchip and multilocus SNPs showed intraclonal diversity with genome rearrangements, variations in pathogenic islands and acquisition of mutations in the muc genes and mutS, muL and uvrD genes of the mismatch repair system (MMR).
To understand the role of hypermutation in the pathogenesis of chronic lung infection and antibiotic resistance, couples of clinical wild type/hypermutable clonally related P. aeruginosa strains and the isogenic laboratory strains PAO1/PAO1∆mutS were subjected to competition in murine model. After 14 days, P. aeruginosa hypermutable strains were less efficient than wild type in establishing chronic lung infection in C57Bl/6 mice. Under antibiotic treatment the results were opposed. In vitro, the hypermutable strains showed a higher level of resistance to 10 antibiotics and the MIC returned back to the level of the wild type strains when complemented with MMR genes.
Our finding suggests that hypermutation is a key factor in development of multiple-antimicrobial resistance and may favor chronic colonization in CF patients under antibiotics treatment.
Supported by the Italian CF Research Foundation
Cost versus benefit of Pseudomonas aeruginosa hypermutation in the absence or presence of antibiotic treatment
No full textStressful conditions in patients with cystic fibrosis (CF) are thought to select P. aeruginosa hypermutable clones with mutations in genes of the mismatch repair system (MRS) by hitchhiking with adaptive mutations. Whether the increased mutation rate of P. aeruginosa hypermutable strains is associated with a biological benefit or cost for the colonization of secondary environments is not known. We have previously showed that P. aeruginosa increased mutagenesis is associated with an important biological cost reducing the potential for the colonization of new environments in the absence of selective pressure when tested in a mouse model of chronic infection (Montanari et al, Pediatric Pulmonology 28, 2005; abstract nr 287). Here, we compared those results in the presence of selective pressure such as antibiotic treatments.
Couples of clinical hypermutable/wild type clonally related P. aeruginosa strains, the laboratory strains PAO1∆mutS/PAO1 and the strains complemented with plasmids containing genes involved in the MRS (mutS, mutL and uvrD) were subjected to competition in vitro and in vivo in the presence or absence of antibiotics. In vitro, in the presence of streptomycin (STR 100g/ml) or nalidixic acid (NAL 200g/ml), the hypermutable outcompeted the wild type and its complemented strains in the laboratory strain PAO1 (competition index (CI) (PAO1∆mutS/PAO1)/ (PAO1∆mutS mutS+/PAO1): 1.4 in streptomycin and 1.25 in nalidixic acid) and in the P. aeruginosa clinical clonal pairs tested in NAL (CI (BST44/BST2)/(BST44mutS+/BST2): 2.3; (RP74/RP73)/(RP74mutL+/RP73): 7.1; (MF2/MF1)/(MF2uvrD+/MF1): 10.1). In the absence of antibiotic pressure, three hypermutable strain(s) were disadvantaged (CI (PAO1∆mutS/PAO1)/ (PAO1∆mutS mutS+/PAO1): 0.25; (BST44/BST2)/(BST44mutS+/BST2): 0.4; (RP74/RP73)/(RP74mutL+/RP73): 0.54) and one decreased its advantage (MF2/MF1)/(MF2uvrD+/MF1): 4.1).
To show that the advantage of the P. aeruginosa strains is not caused by increased resistance, the MICs for STR and NAL were determined. Although the hypermutable strains showed a higher level of resistance to the antibiotics, the MICs returned back to the level of the wild type strains when complemented with the wild type copy of MRS gene. These data indicated that the resistant phenotype was developed in vitro after antibiotic exposure and was not caused by stable mutations during previous exposures in the CF patient’s lung.
Competition experiments between PAO1∆mutS/PAO1 were performed in the agar beads mouse model for chronic airway infection. Under streptomycin treatment for 14 days, the hypermutable strain PAO1∆mutS was more efficient to establish a murine chronic infection when compared to its wild type parent strain (CI PAO1∆mutS/PAO1: 2.97) while in the absence of antibiotic treatment the results were opposed (CI: 0.002).
The results suggest that P. aeruginosa increased mutagenesis, associated with an important biological cost in the absence of selective pressure, turn to a benefit in the presence of strong selective pressure such as antibiotic treatments.
Supported by the Italian CF Research Foundation and Associazione Lombarda FC
Evaluation of the biological cost of Pseudomonas aeruginosa hypermutation in a murine model of chronic pulmonary infection
No full text
Pathogenecity of Pseudomonas aeruginosa clonal strains isolated from CF patients in a murine model of chronic pulmonary infection
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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